This invention relates to the development of an improved method of preparing trifluoromethylthiocopper in a colorless solid state, its stability and use in the synthesis of biologically and pharmacologically active organic and inorganic compounds incorporating the trifluoromethylthiyl group.
Although the chemistry of trifluoromethylthiyl group dates back to 1939 ((a) French Patent 503,920 (1939), (b) O. Scherrer, Angew. Chem., 52, 457, (1939)), interest in this functional group remained dormant until the synthesis of bis(trifluoromethyl) disulfide ((a) F. W. Bennett, G. R. A. Brandt, H. J. Emeleus and R. N. Haszeldine, Nature, 116, 225, 1950. (b) G. R. A. Brandt, H. J. Emeleus and R. N. Haszeldine, J. Chem. Soc., 2198, 1952.). Since then, bis(trifluoromethyl) disulfide has been prepared by various procedures ((a) M. Haupstschein and A. V. Grosse, J. Am. Chem. Soc., 73, 5461, 1951, (b) R. N. Haszeldine and J. M. Kidd, J. Chem. Soc., 3219, 3223, 1953. (c) E. Kober, J. Am. Chem. Soc., 81, 4810, 1959. (d) E. Mann, D. D. Coffman and E. L. Mutterties, J. Am. Chem. Soc., 81, 3575, 1959. (e) H. J. Emeleus and A. Hass, J. Chem. Soc., 1271, 1963. (f) H. Kloosterzeil, Rec. trav. Chem. (Holland), 82, 497, 1963.). In fact, it is the synthesis of bis(trifluoromethylthio)mercury from the trifluoromethylthiyl group that provided the impetus for the renewal of interest in the chemistry of trifluoromethylthiyl group ((a) G. R. A. Brandt, H. J. Emeleus and R. N. Haszeldine, J. Chem. Soc., 1298, 1952. (b) E. Mann, D. D. Coffman and E. L. Mutterties, J. Am. Chem. Soc., 81, 3575, 1959). The first report of trifluoromethylthiocopper was its in situ preparation from bis(trifluoromethylthio)mercury and copper powder ((a) W. C. Randall, P. S. Anderson, E. L. Cresson, C. A. Hunt, T. F. Lyon, K. E. Rittle, D. C. Remy, J. P. Springer, J. M. Hirsfield, K. Hoogsteen, M. Williams, E. A. Risley, and J. A. Totaro, J. Med. Chem., 22, 1222, 1979 (and references cited therein). (b) D. C. Remy, K. E. Ritchie, C. A. Hunt and M. B. Freedman, J. Org. Chem., 41, 1645, 1976. (c) D. C. Remy, K. E. Kittle, C. A. Hunt, P. S. Anderson, B. A. Arison, E. I. Engelhardt, B. V. Clineschmidt, V. J. Lotti, P. R. Bunting, R. J. Ballentine, N. L. Popp, L. Flataker, J. J. Witosiawski, and C. A. Stone, J. Med. Chem., 20, 1013, 1977. (d) R. D. Dresden in "Fluorine Chemistry Reviews," Vol. IV, P. Tarrant(Ed), Marcel Decker, Inc., New York (1969). (e) E. A. Nadiff, S. Lapschutz, P. N. Craig and M. Gordon, J. Org. Chem., 25, 60, 1960. (f) E. Mann, D. D. Coffman and E. L. Mutterties, J. Am. Chem. Soc., 81, 3575, 1959). Our own interest in the trifluoromethylthiyl group was kindled by a report that this functionality significantly altered the pharmacological properties of the parent compound and endowed it with antipsychotic properties (D. C. Remy, K. E. Kittle, C. A. Hunt, P. S. Anderson, B. A. Arison, E. I. Engelhardt, B. V. Clineschmidt, V. J. Lotti, P. R. Bunting, R. J. Ballentine, N. L. Popp, L. Flataker, J. J. Witoslawski, and C. A. Stone, J. Med. Chem., 20, 1013, 1977). Thus the introduction of trifluoromethylthiyl moiety in the 3-position of cycloheptadienes enhanced their pharmacological properties and binding to molecular receptors (D. C. Remy, K. E. Kittle, C. A. Hunt, P. S. Anderson, B. A. Arison, E. I. Engelhardt, B. V. Clineschmidt, V. J. Lotti, P. R. Bunting, R. J. Ballentine, N. L. Popp, L. Flataker, J. J. Witoslawski, and C. A. Stone, J. Med. Chem., 20, 1013, 1977). Additional biological properties have been attributed to the trifluoromethylthiyl group (R. D. Dresden in "Fluorine Chemistry Reviews," vol. IV, P. Tarrant(Ed), Marcel Decker, Inc., New York (1969). (e) E. A. Nadiff, S. Lapschutz, P. N. Craign and M. Gordon, J. Org. Chem., 25, 60, 1960). The trifluoromethylthiyl group has, for the same reason, been incorporated into various novel heterocyclic systems ((a) M. R. C. Gerstenberger, A. Haas and F. Liebig, J. Fluorine Chem., 25, 60, 1960. (b) D. M. Mulvey and H. Jones, J. Heterocyclic Chem., 12, 597, 1975). In connection with other on-going projects in or laboratory, large quantities of trifluoromethylthiocopper were required. After several unsuccessful attempts to prepare trifluoromethylthiocopper according to the published procedure (N. V. Kondratecnko, A. A. Kolomeytsev, V. I. Popov and L. M. Yagupolskii, Synthesis 667, 1985), we explored several solvents such as diethyl ether, diisopropyl ether and tetrahydrofuran. Realizing that solvents having high dielectric constants are better suited to form a complex with trifluoromethylthiocopper and that it may precipitate out by itself from a concentrated solution, we then attempted to prepare trifluoromethylthiocopper as a complex of acetonitrile. Our expectation was rewarded.